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Oxytocin regulates body composition.

Li Sun1,2, Daria Lizneva1,2, Yaoting Ji1,2,3

  • 1The Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029.

Proceedings of the National Academy of Sciences of the United States of America
|December 18, 2019
PubMed
Summary
This summary is machine-generated.

Oxytocin (OXT) directly impacts bone health by stimulating osteoblasts and regulating osteoclasts. This research reveals OXT

Keywords:
adipose tissuebone phenotypeconditional knockoutpituitary hormone

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Area of Science:

  • Endocrinology and Bone Biology
  • Metabolic Regulation and Obesity

Background:

  • Oxytocin (OXT), a neurohypophyseal nonapeptide, is known for roles in parturition, lactation, appetite, and social behavior.
  • Emerging evidence suggests OXT influences the mammalian skeleton, affecting bone formation and resorption.
  • The precise mechanisms and cellular targets of OXT in bone metabolism and body composition remain incompletely understood.

Purpose of the Study:

  • To elucidate the direct roles of oxytocin receptors (OXTRs) in osteoblasts and osteoclasts in vivo.
  • To investigate the contribution of OXT to bone mass regulation, particularly concerning estrogen effects and pregnancy/lactation.
  • To examine the impact of OXT on adipocyte function and overall body composition, exploring its potential antiobesity effects.

Main Methods:

  • Generation of conditional knockout mouse models (Col2.3Cre:Oxtr and Acp5Cre:Oxtr) to selectively delete OXTRs in osteoblasts and osteoclasts.
  • Phenotypic analysis of bone mass, bone resorption, and bone formation in these genetically modified mice.
  • Assessment of OXT's effects on adipocyte differentiation and body fat content, including in response to OXT administration.

Main Results:

  • Selective deletion of OXTRs in osteoblasts (Col2.3Cre:Oxtr) resulted in low bone mass, highlighting OXT's anabolic role in osteoblasts and its necessity for estrogen's bone-protective effects.
  • Deletion of OXTRs in osteoclasts (Acp5Cre:Oxtr) led to high bone mass, indicating OXT's role in stimulating osteoclastogenesis.
  • OXT was found to inhibit bone resorption during pregnancy and lactation, protecting against bone loss, and to suppress the white-to-beige adipocyte transition, reducing body fat.

Conclusions:

  • Oxytocin exerts significant direct anabolic and anti-resorptive effects on the skeleton via osteoblast and osteoclast OXTRs, respectively.
  • Osteoblastic OXTRs are crucial mediators of estrogen's beneficial effects on bone.
  • OXT's actions on bone and adipocytes suggest its potential as a therapeutic target for osteoporosis and obesity.